African trypanosomiasis impacts both human and animal health in Sub-Saharan Africa. Uganda is the only country that has both forms of the human African trypanosomiasis (HAT): Trypanosoma brucei gambiense (Tbg) in the north-west and Trypanosoma brucei rhodesiense (Tbr) in the south-east. Tbr cases have been migrating from their traditional foci in the south to central Uganda, with the two disease belts feared to merge in northern Uganda. This interdisciplinary project focuses on northern Uganda to understand HAT transmission dynamics and risk of Tbr and Tbg disease merger. Our findings will provide fundamental knowledge on the role of the vector in HAT epidemiology, and provide practical information to inform the development and implementation of effective control strategies. We propose five integrated aims to: 1) Analyze the genomic variation in Gff, its associated microbiome and parasite (Trypanosoma) using a multispecies SNP chip, 2) Characterize the expression and genetic variations of the Trypanosoma-resistance candidate genes in different Gff population groups, 3) Discover gene-environment associations and impacts of climate change on Ugandan Gff, 4) Understand genetic as well as microbiome contributions for differentiation of Gff populations and 5) Assess the impact of Gff dispersal on the effectiveness and cost-effectiveness of vector control for reducing trypanosomiasis burden. Our studies will produce 1) fundamental information on host-parasite interactions that will predict the potential risk of disease merger and its epidemiological consequences, 2) suitability maps for Gff based on genetic and environmental data to better plan and operate vector control activities, 3) candidate genes on parasite-resistance, environmental adaptations that can be used in downstream genetic control methods and 4) predictions on the most effective and cost-effective control methods for HAT.